Monday, 7 July 2014
Summarizing video on Melanoma at ASCO
A good video with Jedd Wolchok:
@ min 11: listen to relationship between PDL1 expression and response to anti-PD1 (in a nutshell, PDL1 expression is neither permanent nor evenly expressed in the tumor, so is NOT a good biomarker for response to anti-PD1 treatment)
@ min 15: the Ipi/ Nivo combo
As always, some *irritating* comments about side effects- untreated Melanoma's side effect is death, so maybe we should start looking at side effects in comparison to the positive effect of the drug: in Melanoma, no drug does not equal no side effects but death, so if Grade 3 side effects are the price to live, which patient will rather die?
Tellingly, the doctor was less worried about them than the interviewer and any speaker I've heard at ASCO said that they had gotten much better at detecting side effects under immuntherapy earlier and gotten better at treating them.
@ ca min 25: the BRAF/ MEK combo- COMBI-D trial from GSK
I had hoped for a personal opinion on why the latest data about the BRAF/MEK combo versus BRAF alone somehow all of a sudden seems to show that the BRAF mono therapy is *better* than in the Phase 2 trial.
Now, drugs in later stage trials somehow always tend to do *worse* than initially assumed, there are articles out there on how early trials tend to overestimate efficacy and underestimate side effects, so now all of a sudden having a drug being *better* is a bit of an oddity and requires an explanation.
There are a number of possibilities out there- including patient selection, differences in evaluation and the time-point of when a patient is taken off a trial- all of them are relevant to patients, because they could tell us things like which patients are more likely to respond or whether PFS (progression-free survival) as a surrogate marker in clinical trials is influenced by the general treatment options available because one of the possible explanations is that doctors kept their patients as long as possible on the trial because there simply were no other treatment options around (the no scan, no progression option).
So simply saying 'we have to wait for more results in the future' is also a way of chickening out- and picking on Jeff Wolchok now is grossly unfair because that's the general refrain.
However, Melanoma patients continue to die and our patients have already lost their lives on these trials, so they deserve the most open trouble-shooting discussion everyone can come up with.
Science is by definition not a straight path but trial and error- but progress depends on the quality of the trouble-shooting. While expecting that every experiment succeeds is unrealistic, patients can expect that there is an open and constructive discussion about what didn't work to ensure the fastest progress possible- because they paid and continue to pay with their lives for that very research.
As Helsinki states
6. The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments).
The fastest way of understanding is not to NOT talk about it!